Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Proteins.
Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170, HspBP1/Sil1, and BAG Domain Proteins.
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DOI：
10.1007/978-3-031-14740-1_1
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发表时间：
2023-01-01
影响因子：
--
通讯作者：
Verghese, Jacob
中科院分区：
文献类型：
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作者：
Bracher, Andreas;Verghese, Jacob
Hsp70家族的分子伴侣是细胞蛋白折叠机制的关键组成部分。底物折叠是通过ATP结合、水解和释放的迭代循环完成的。Hsp70的atp酶活性受两类主要的伴侣蛋白调控：j结构域蛋白刺激Hsp70水解atp酶，而核苷酸交换因子（nef）促进从adp结合状态到atp结合状态的转化，从而关闭伴侣蛋白折叠循环。另外，ADP解离抑制剂可拮抗NEF功能。从发现典型的细菌NEF GrpE开始，Hsp70的核苷酸交换因子的多样性已经被确定，将其与真核细胞中的许多细胞过程联系起来。本文综述了Hsp110/Grp170、HspBP1/Sil1和BAG结构域蛋白家族的核苷酸交换因子的结构和功能的最新进展，并讨论了这些辅伴侣蛋白如何将蛋白质折叠与细胞质量控制和降解途径联系起来。
Molecular chaperones of the Hsp70 family are key components of the cellular protein-folding machinery. Substrate folding is accomplished by iterative cycles of ATP binding, hydrolysis, and release. The ATPase activity of Hsp70 is regulated by two main classes of cochaperones: J-domain proteins stimulate ATPase hydrolysis by Hsp70, while nucleotide exchange factors (NEFs) facilitate the conversion from the ADP-bound to the ATP-bound state, thus closing the chaperone folding cycle. NEF function can additionally be antagonized by ADP dissociation inhibitors. Beginning with the discovery of the prototypical bacterial NEF, GrpE, a large diversity of nucleotide exchange factors for Hsp70 have been identified, connecting it to a multitude of cellular processes in the eukaryotic cell. Here we review recent advances toward structure and function of nucleotide exchange factors from the Hsp110/Grp170, HspBP1/Sil1, and BAG domain protein families and discuss how these cochaperones connect protein folding with cellular quality control and degradation pathways.